Acidic Nanoparticles Prevent HIV Pre‐Exposure Prophylaxis (PrEP)‐Induced Oligodendrocyte Impairments by Restoring Lysosomal pH in Adolescent Models

Caela C. Long; Lindsay K. Festa; Melanie Cruz‐Berrios; Teshawn D. Johnson; Claire Mitchell; Kelly L. Jordan‐Sciutto; Judith B. Grinspan

doi:10.1002/glia.70050

journal article Open Access Jul 17, 2025

Acidic Nanoparticles Prevent HIV Pre‐Exposure Prophylaxis (PrEP)‐Induced Oligodendrocyte Impairments by Restoring Lysosomal pH in Adolescent Models

Caela C. Long

Lindsay K. Festa

Melanie Cruz‐Berrios Teshawn D. Johnson Claire Mitchell

Kelly L. Jordan‐Sciutto Judith B. Grinspan

Glia Vol. 73 No. 10 pp. 1967-1988 · Wiley

View at Publisher Save 10.1002/glia.70050

Abstract

ABSTRACTA disproportionate percentage of adolescents are diagnosed with human immunodeficiency virus (HIV) in the United States each year. Preexposure prophylaxis (PrEP), an antiretroviral regimen, is effective at preventing the transmission of HIV to adolescents at substantial risk for acquiring HIV. However, other select antiretrovirals have been shown to cause white matter deficits in experimental models. Adolescents taking PrEP are uniquely vulnerable to myelin impairments as the adolescent brain undergoes high rates of myelination. Here, we report that PrEP significantly reduced oligodendrocyte maturation in adolescent rats. Furthermore, cultures of primary rat oligodendrocyte progenitors treated with PrEP showed inhibited oligodendrocyte differentiation through deacidification of lysosomes resulting in lysosomal accumulation of myelin proteins. Acidic nanoparticle co‐administration with PrEP prevented PrEP‐induced oligodendrocyte maturation impairments both in vivo and in vitro. These studies suggest uninfected adolescents are vulnerable to PrEP‐induced oligodendrocyte impairments and identify maintenance of lysosome pH as a critical factor in antiretroviral design.

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Details

Published: Jul 17, 2025
Vol/Issue: 73(10)
Pages: 1967-1988
License: View

Authors

C

Caela C. Long

Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA

L

Lindsay K. Festa

Children's Hospital of Philadelphia Philadelphia Pennsylvania USA

M

Melanie Cruz‐Berrios

Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA

T

Teshawn D. Johnson

Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA

C

Claire Mitchell

University of Pennsylvania School of Dental Medicine Philadelphia Pennsylvania USA

K

Kelly L. Jordan‐Sciutto

University of Pennsylvania School of Dental Medicine Philadelphia Pennsylvania USA

J

Judith B. Grinspan

Children's Hospital of Philadelphia Philadelphia Pennsylvania USA

Funding

National Institutes of Health Award: F31 MH128135

Multiple Sclerosis Society Award: TA‐2204‐39435

Cite This Article

Caela C. Long, Lindsay K. Festa, Melanie Cruz‐Berrios, et al. (2025). Acidic Nanoparticles Prevent HIV Pre‐Exposure Prophylaxis (PrEP)‐Induced Oligodendrocyte Impairments by Restoring Lysosomal pH in Adolescent Models. Glia, 73(10), 1967-1988. https://doi.org/10.1002/glia.70050

Acidic Nanoparticles Prevent HIV Pre‐Exposure Prophylaxis (PrEP)‐Induced Oligodendrocyte Impairments by Restoring Lysosomal pH in Adolescent Models

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